Interactive responses in gut immunity, and systemic and local changes in the insulin-like growth factor system in nursery pigs in response to Salmonella enterica serovar Typhimurium,

Abstract

Abstract In recent years, we have sought to understand how disparate endocrine and immune signals converge in response to Salmonella enterica serovar Typhimurium (ST) to affect growth and the IGF system in the nursery pig. The enteric pathogen ST interacts with gut epithelium to rapidly upregulate the chemoattractive chemokines IL-8 and chemokine ligand-20, and to selectively affect toll-like receptors. Activation of these components of the innate immune system seems to confine the immune response largely to the gut mucosa and mesenteric lymph nodes, as evidenced by the lack of systemic elevation of proinflammatory cytokines. Despite the apparent restriction of proinflammatory signals to the gut-associated lymphoid tissue, ST provokes peripheral sequelae consistent with danger signaling, including the febrile response and activation of the adrenal axis. In addition, pigs undergoing ST-induced febrile responses experience a consistent period of inappetence that is independent of changes in leptin. Moreover, this period of decreased intake is invariably accompanied by an unmistakable decrease in serum IGF-I and, less consistently, with parallel reductions in circulating IGFBP-3. More recently, we characterized changes in expression of components of the IGF system within skeletal muscle of pigs undergoing ST-associated enteric disease. Despite the characteristic decrease in circulating IGF-I, the relative abundance of skeletal muscle IGF-I and IGFBP-3 mRNA was unaffected by ST. However, mRNA for IGFBP-5 was decreased in the skeletal muscle of ST-challenged pigs, suggesting a possible effect of the enteric disease on IGF availability. Taken together, oral challenge with ST engages elements of the mucosal innate immune system that seem to contain the spread of systemic proinflammatory cytokine signals. Even so, ST challenge is associated with parallel changes in both systemic and local IGF systems that may affect pig growth.